Increase of IgA-bearing Peripheral Blood Lymphocytes in Families of Patients with IgA Nephropathy

Abstract

IgA-bearing peripheral blood lymphocytes, serum IgA, urinary sediments and HLA types of patients with IgA nephropathy and members of their families were examined to elucidate whether some familial factors might be related to the development of IgA nephropathy. Ten patients with IgA nephropathy, 31 family members and 36 age-matched healthy persons were examined. All families included certain members with increased amounts of IgA-bearing peripheral blood lymphocytes. The pattern of the emergence of family members with increased IgA-bearing lymphocytes was vertical. Some family members who had increased IgA-bearing lymphocytes showed microhematuria at the time of the study. There was no significant correlation between the amounts of IgA-bearing peripheral blood lymphocytes and levels of serum IgA. HLA types of the ten patients did not show significant deviation from those in the general population. It is suggested that the measurement of IgA-bearing peripheral blood lymphocytes among family members is useful for the screening of patients with IgA nephropathy.

Polymeric IgA1 from Patients with IgA Nephropathy Upregulates Transforming Growth Factor-β Synthesis and Signal Transduction in Human Mesangial Cells via the Renin-Angiotensin System

“…The disease is characterized by mesangial deposition of polymeric IgA1 (pIgA1), proliferation of mesangial cells, increased synthesis of extracellular matrix, and infiltration by macrophages, monocytes, and T cells (2). Immunoregulatory abnormalities involving IgA1 synthesis in IgAN include overproduction of IgA1 by B lymphocytes in vitro (3,4), increased serum levels of IgA, IgA-containing immune complexes (5,6), and anionic IgA (7), and abnormal glycosylation of the carbohydrate moieties in IgA1 from these patients (8). Five different IgA receptors have been identified in human subjects, including Fc␣R1 or CD89, the polymeric Ig receptor, the asialoglycoprotein receptor, Fc␣/ R, and the transferrin receptor or CD71.…”

Abnormalities of the IgA immune system in members of unrelated pedigrees from patients with IgA nephropathy

“…The cell suspension recovered at the interface was resuspended in RPMI 1640 (Eurobio, Paris, France) and supplemented with penicillin (100 U/ml), streptomycin (100 ,ug/ml), glutamine (2 mM) and 10% heat-inactivated fetal calf serum (FCS). PBMC at a concentration of 2 x 106 cells/ ml were stimulated with pokeweed mitogen (PWM), 5 (Fig. la).…”

“…Although systematic screening urinalysis testing in family members of patients with glomerulonephritis is not a common practice for nephrologists, in the last few years many investigators have reported the occurrence of IgAN or the presence of persistent microscopic haematuria and/or proteinuria in family members of patients with this disease [5][6][7][8][9]. Therefore, two forms of disease have been identified as follows: (i) familial IgAN, characterized by the presence of the disease in siblings or other first-degree relatives; (ii) sporadic IgAN, occurring only in one member of the family [10].…”

“…Several studies have described various immune abnormalities involving the regulation of IgA synthesis in relatives of IgAN patients [5][6][7][10][11][12]. To our knowledge, no extensive Correspondence: Prof. F. P. Schena, Chair of Nephrology, Polyclinic, Piazza G. Cesare 11, 1-70124 Bari, Italy studies have been performed concerning the production of pIgA and IgA RF by PBMC in relatives of IgAN patients.…”

Profiles of immunoregulatory cytokine production in vitro in patients with IgA nephropathy and their kindred

“…Immunological abnormalities that mimic those found in patients have been described in their healthy relatives [20][21][22][23][24]. From our recent investigations [9,10,[25][26][27], we hypothesized that the immunoregulatory defect that underlies the disease might be, at least partially, genetically determined, and that the immune background described in patients should in some way appear in the familial background.…”